Trisomy 6p and ring chromosome 11 in a melanotic schwannoma suggest relation to malignant melanoma rather than conventional schwannoma

Melanotic schwannoma is a rare entity that generally occurs in young adults and commonly arises from the sympathetic nervous system even if soft tissue and visceral organs can also be affected [1]. Although most cases are benign, the outcome of this tumor is difficult to predict. Indeed, 15% of the reported patients have died of metastatic disease [1]. We report here the first cytogenetic description of a case of malignant melanotic schwannoma. A 47-year-old male presented with abdominal pain of 2 months duration. A computed tomography scan of the abdomen revealed a 19 9 17 9 10 cm retroperitoneal mass involving the small intestine, the bladder and the left diaphragm. A biopsy was performed. Histological examination showed a proliferation mainly made up of spindle cells and a component of epithelioid cells (Fig. 1a). In some areas, spindles cells were arranged in fascicles mimicking the architecture of a schwannoma. The cytoplasm of some cells contained brown pigment positively labeled by the Masson Fontana silver stain for melanin. The nuclei were uniform showing only mild atypia and some of them containing small nucleoli. The number of mitosis was very low (1 at Gx400/10 fields). The tumor cells were strongly and diffusely positive for S-100 protein, HMB-45, and negative for EMA, CD34, chromogranin A and actin (Fig. 1b). There was no clinical evidence of primary cutaneous or gastrointestinal melanoma. Therefore, a diagnosis of melanotic schwannoma was established. Clinical workup for the manifestations of the Carney complex was performed and included screening for cardiac myxomas, pigmentation abnormalities, and endocrine diseases. No abnormality was observed and the melanotic schwannoma was considered as sporadic. The patient underwent surgery, which was not radical because of vascular involvement. The disease progressed during 2 months following surgery. Palliative chemotherapy was started with stable disease as best tumor response. Three years later, the patient developed liver metastasis. He died from progressive metastatic disease 4 years after initial diagnosis. A fresh fragment was prepared for cytogenetic analysis. The RHG-banded karyotype showed a ring chromosome 11 and additional material on the short arm of chromosome 14 suspected to originate from the short arm of chromosome 6 (Fig. 1c). Fluorescence in situ hybridization (FISH) with whole chromosomes painting (WCP) probes for chromosomes 6 and 11 was performed according to the manufacturer’s instructions (Q-BIOgene, Illkirch, France). These experiments confirmed the chromosome 11 origin of the ring chromosome as well as the composition of the derivative chromosome consisting of the short arm of chromosome 6 and long arm of chromosome 14 (Fig. 1d). This unbalanced whole-arm translocation resulted in trisomy 6p. The karytoype was: A. Italiano A.-C. Peyron F. Pedeutour Laboratory of Solid Tumors Genetics, Faculty of Medicine, Nice University Hospital, Nice, France